Herpes simplex virus type 1 in brain and risk of Alzheimer's disease.

Abstract

BACKGROUND:

The apolipoprotein E epsilon 4 (APOE-epsilon 4) allele is a risk factor for Alzheimer's disease (AD), but it is neither essential nor sufficient for development of the disease. Other factors-genetic or environmental-must therefore have a role. By means of a PCR we have detected herpes simplex virus type 1 (HSV1) in latent form in brains of elderly people with and without AD. We have postulated that limited reactivation of the virus causes more damage in AD patients than in elderly people without AD because of a difference in the hosts. We now report the APOE genotypes of AD patients and non-AD sufferers with and without HSV1 in brain.

FINDINGS:

By multiple logistic regression, the APOE-epsilon 4 allele frequency was significantly higher in the patients positive for HSV1 in brain than in the HSV1-negative AD group, the HSV1-positive non-AD group, or the HSV1-negative non-AD group (52.8% vs 10.0%, 3.6%, and 6.3%, respectively). The odds ratio for APOE-epsilon 4 in the HSV1-positive AD group compared with HSV1-negative non-AD group was 16.8 (95% CI 3.61-77.8) and in the HSV1-negative AD group, 1.67 (0.21-13.4). We also compared APOE genotypes of 40 people who had recurrent cold sores and 33 non-sufferers; the APOE-epsilon 4 allele frequencies were 36% and 9%, respectively (p < 0.0001).

INTERPRETATION:

These findings suggest that the combination of HSV1 in brain and carriage of an APOE-epsilon 4 allele is a strong risk factor for AD, whereas either of these features alone does not increase the risk of AD. The findings in people with cold sores support our hypothesis that APOE-epsilon 4 and HSV1 together are damaging in the nervous system.